Excess Risk Of Cardiovascular Disease Research Articles

Presence and Determinants of Cardiovascular Disease and Mortality in Individuals With Type 1 Diabetes of Long Duration: The FinnDiane 50 Years of Diabetes Study.

The aim of this study was to determine the incidence of cardiovascular disease (CVD) and mortality as well as their risk factors in type 1 diabetes (T1D) of >50 years' duration. From 5,396 individuals included in the Finnish Diabetic Nephropathy Study (FinnDiane), 729 diagnosed in 1967 or earlier survived with T1D for >50 years. In this FinnDiane 50-year cohort, cumulative incidence of CVD events was assessed from the diagnosis of diabetes, and the excess CVD risk, compared with 12,710 matched individuals without diabetes. In addition, risk factors for different types of CVD (both nonfatal and fatal) and mortality were analyzed, and cause-specific hazard ratios were estimated during a median follow-up of 16.6 years from the baseline visit (median duration of diabetes 39 years at baseline). In individuals with diabetes duration of >50 years, the 60-year cumulative incidence of CVD from the diagnosis of diabetes was 64.3% (95% CI 62.5-66.0). Compared with individuals without diabetes, the standardized incidence ratio for CVD was 7.4 (6.5-8.3); in those with normoalbuminuria, it was 4.9 (4.0-5.9). Mean HbA1c and HbA1c variability, dyslipidemia, BMI, kidney disease, age, and diabetes duration were the variables associated with incident CVD. In particular, HbA1c was associated with peripheral artery disease (PAD). The standardized mortality ratio compared with the Finnish background population was 3.2 (2.8-3.7). The factors associated with mortality were diabetes duration, increased HbA1c variability, inflammation, insulin resistance, kidney disease, and PAD. Individuals with T1D of very long duration are at a high risk of CVD. In addition, throughout the lifespan, optimal glycemic control remains central to CVD and excess mortality prevention.

Long-term population-based trends in the incidence of cardiovascular disease in individuals with type 1 diabetes from Finland: a retrospective, nationwide, cohort study

Cardiovascular disease is the main determinant of premature mortality in patients with type 1 diabetes. However, time trends regarding different types of cardiovascular disease in childhood-onset type 1 diabetes with a long timespan from the diagnosis of diabetes are not well established. This study aimed to investigate the cumulative incidence of cardiovascular disease in individuals with type 1 diabetes in a population-based cohort in Finland, the country with the world's highest incidence of type 1 diabetes. In this retrospective, nationwide registry-based, cohort study, all patients who were diagnosed between Jan 1, 1965, and Dec 31, 1999 with type 1 diabetes when they were younger than 15 years old in Finland were followed up and monitored for the occurrence of cardiovascular disease (including coronary artery disease, stroke, peripheral artery disease, and heart failure) until the end of 2016 and for cardiovascular disease mortality until 2017. Cumulative incidences of cardiovascular disease were calculated by the Fine and Gray method according to the year of diabetes diagnosis using six diagnosis cohorts: 1965-69, 1970-74, 1975-1979, 1980-84, 1985-89, 1990-94, and 1990-95. Trends in cardiovascular disease event rates were analysed by Fine and Gray competing risks regression models using year of diabetes diagnosis as continuous variable. In addition, non-linearity in trends was assessed with restricted cubic splines. The excess risk of coronary artery disease and stroke was estimated by comparison with the risk in the Finnish general population by calculating standardised incidence ratios (SIRs) and their time trends. The data for Finnish general population were drawn from the Cardiovascular Disease Register of the National Institute of Health and Welfare. The SIRs were calculated as ratios of observed and expected number of events in individuals with type 1 diabetes during 1991-2014. 11 766 individuals were included in this study. During 361 033 person-years of follow-up and a median of 29·6 years (IQR 22·3-37·9) follow-up, a total of 1761 individuals had single or multiple types of cardiovascular disease events. 2686 events (864 [32·2%] coronary artery disease events, of which 663 were acute myocardial infarctions; 497 [18·5%] strokes; 854 [31·8%] peripheral artery diseases, of which 498 were lower extremity amputations; and 471 [17·5%] heart failure events) were reported until Dec 31, 2016, and 1467 deaths until Dec 31, 2017. Cardiovascular disease risk decreased linearly by 3·8% (hazard ratio [HR] 0·96 [95% CI 0·96-0·97]; p<0·0001) by later calendar year of diabetes diagnosis (p<0·0001). There was a decrease in the SIRs for both coronary artery disease and stroke within all 10-year age groups under 65 years, except for stroke in the oldest age group. However, the SIR was still 8·9 (95% CI 3·9-17·5) for coronary artery disease and 2·9 (1·3-5·7) for stroke in those diagnosed with type 1 diabetes in the 1990s. Finally, the cardiovascular disease death rate decreased constantly by diagnosis year. The risk of cardiovascular disease has decreased over time in Finland in individuals with childhood-onset type 1 diabetes. However, there is still considerable excess cardiovascular disease risk in individuals with type 1 diabetes compared with the general population. These results highlight the need for studies on the mechanisms of atherosclerosis from the time of diagnosis of type 1 diabetes to facilitate early and effective prevention of cardiovascular disease in these individuals. Folkhälsan Research Foundation, Academy of Finland, Wilhelm and Else Stockmann Foundation, Liv och Hälsa Society, Novo Nordisk Foundation, Finnish Foundation for Cardiovascular Research, Finnish Diabetes Research Foundation, Diabetes Research Foundation, Medical Society of Finland, Sigrid Jusélius Foundation, and Helsinki University Hospital Research Funds.

Prevalence and risk factors of peripheral artery disease in a population with chronic kidney disease in Australia: A systematic review and meta‐analysis

There is a lack of clarity and guidance for screening peripheral artery disease (PAD) in persons with chronic kidney disease (CKD) and end stage kidney disease (ESKD) despite this group being at excess risk of cardiovascular disease (CVD). In this current study, we performed a systematic review and meta-analysis to examine the prevalence and risk factors for PAD in persons with CKD in Australian cohorts. We used the inverse variance heterogeneity meta-analysis with double arcsine transformation to summarize the prevalence of PAD (with 95% CIs). Nine studies and 18 reports from the Australia and New Zealand dialysis and transplant registry with 36 cohorts were included in the review. We found a substantially higher PAD prevalence in cohorts based on an ankle-brachial index (ABI) or toe systolic pressure (TBI) than cohorts based on self-reported history. Higher PAD prevalence was observed in ESKD persons than CKD persons without dialysis (PAD diagnosis based on ABI or TBI: 31% in ESKD persons and 23% in CKD persons, PAD diagnosis based on self-reported history: 17% in ESKD persons and 10% in CKD persons). Older age, Caucasian race, cerebrovascular disease and haemodialysis were associated with the presence of PAD in ESKD persons. Our findings indicated a considerable proportion of PAD in CKD and ESKD persons particularly in those with ESKD. To develop and provide an adequate plan to clinically manage CKD patients with PAD, evidence of cost-effectiveness and clinical benefit of early detection of PAD in persons with CKD in Australia is recommended for future studies.

Association of Syndemic Unhealthy Alcohol Use, Smoking, and Depressive Symptoms on Incident Cardiovascular Disease among Veterans With and Without HIV-Infection.

Unhealthy alcohol use, smoking, and depressive symptoms are risk factors for cardiovascular disease (CVD). Little is known about their co-occurrence - termed a syndemic, defined as the synergistic effect of two or more conditions-on CVD risk in people with HIV (PWH). We used data from 5621 CVD-free participants (51% PWH) in the Veteran's Aging Cohort Study-8, a prospective, observational study of veterans followed from 2002 to 2014 to assess the association between this syndemic and incident CVD by HIV status. Diagnostic codes identified cases of CVD (acute myocardial infarction, stroke, heart failure, peripheral artery disease, and coronary revascularization). Validated measures of alcohol use, smoking, and depressive symptoms were used. Baseline number of syndemic conditions was categorized (0, 1, ≥ 2 conditions). Multivariable Cox Proportional Hazards regressions estimated risk of the syndemic (≥ 2 conditions) on incident CVD by HIV-status. There were 1149 cases of incident CVD (52% PWH) during the follow-up (median 10.1years). Of the total sample, 64% met our syndemic definition. The syndemic was associated with greater risk for incident CVD among PWH (Hazard Ratio [HR] 1.87 [1.47-2.38], p < 0.001) and HIV-negative veterans (HR 1.70 [1.35-2.13], p < 0.001), compared to HIV-negative with zero conditions. Among those with the syndemic, CVD risk was not statistically significantly higher among PWH vs. HIV-negative (HR 1.10 [0.89, 1.37], p = .38). Given the high prevalence of this syndemic combined with excess risk of CVD, these findings support linked-screening and treatment efforts.

An audit into the management of diabetes mellitus at Broadmoor Hospital

AimsDiabetes mellitus confers a twofold excess risk of cardiovascular disease - the leading cause of premature mortality in those with severe mental illness. Inpatients in forensic settings often have more severe, enduring and treatment-resistance forms of mental illness, sometimes necessitating combinations of prescribed antipsychotics. This audit aimed to assess adherence to National Institute for Health and Care Excellence (NICE) guidelines NG28 titled “type 2 diabetes in adults: management” and summarise the metabolic parameters of those with diabetes mellitus at Broadmoor hospital.MethodThis was a retrospective audit in a high secure forensic psychiatry hospital in the United Kingdom, into the management of patients with diabetes mellitus compared to guidance from NICE (NG28).ResultWe report data from over 30 inpatients (out of approximately 200) at a high secure forensic psychiatry hospital with a diagnosis of type 2 diabetes mellitus across two audit cycles. This audit identified improved adherence to national guidance regarding six monthly monitoring of HbA1c but with less than 50% of such patients having an HbA1c at or below the recommended target. This is in addition to high rates of other metabolic disorders such as obesity, dyslipidaemia and hypertension and a mean QRISK3 score that was markedly higher than a healthy person with the same age, sex, and ethnicity. There was a prevalence of background diabetic retinopathy of 8%, diabetic nephropathy of 5.4%, no recorded cases of diabetic neuropathy and a macrovascular disease prevalence of 5.4%. There were no new diagnoses of microvascular or macrovascular disease between audit cycles. One of the key changes between audit cycles was the recruitment of a dietician to the hospital. By the time of undertaking the second audit cycle, 23 patients had documented evidence of having been offered a referral to the dietician.ConclusionThis audit highlighted the marked cardiovascular risk in patients with type 2 diabetes mellitus at a high secure forensic psychiatry hospital. This includes suboptimal control of blood pressure, lipid profiles and HbA1c that increases the risk of premature mortality in these patients with severe mental illness. Wider, cultural changes in practice need to be implemented to improve the metabolic health of patients in the long-term inpatient setting of Broadmoor Hospital. This includes prescribers avoiding the most diabetogenic antipsychotics where possible, increasing the provision of sugar-free options at the on-site shop, examining the proportion of carbohydrate-rich foodstuffs in the shop and understanding the characteristics of its heaviest purchasers, and continued coordination between primary care and ward teams to support patients in making sustained changes to improve their metabolic health.

Sex-specific differences in left ventricular mass and myocardial energetic efficiency in non-diabetic, pre-diabetic and newly diagnosed type 2 diabetic subjects

BackgroundWomen with type 2 diabetes (T2DM) have a higher excess risk for cardiovascular disease (CVD) than their male counterparts. However, whether the risk for CVD is higher in prediabetic women than men is still debated. We aimed to determine whether sex-related differences exist in left ventricular mass index (LVMI), and myocardial mechano-energetic efficiency (MEEi) in with normal glucose tolerant (NGT), pre-diabetic and newly diagnosed type 2 diabetic subjects.MethodsSex-related differences in LVMI and myocardial MEEi, assessed by validated echocardiography-derived measures, were examined among 1562 adults with NGT, prediabetes, and newly diagnosed T2DM, defined according to fasting glucose, 2-h post-load glucose, or HbA1c.ResultsWorsening of glucose tolerance in both men and women was associated with an increase in age-adjusted LVMI and myocardial MEEi. Women with newly diagnosed T2DM exhibited greater relative differences in LVMI and myocardial MEEi than diabetic men when compared with their NGT counterparts. Prediabetic women exhibited greater relative differences in myocardial MEEi, but not in LVMI, than prediabetic men when compared with their NGT counterparts. The statistical test for interaction between sex and glucose tolerance on both LVMI (P < 0.0001), and myocardial MEEi (P < 0.0001) was significant suggesting a sex-specific association.ConclusionsLeft ventricle is subject to maladaptive changes with worsening of glucose tolerance, especially in women with newly diagnosed T2DM. The sex-specific increase in LVM and decrease in MEEi, both being predictors of CVD, may have a role in explaining the stronger impact of T2DM on the excess risk of CVD in women than in men.

Isolated systolic and diastolic hypertension by the 2017 American College of Cardiology/American Heart Association guidelines and risk of cardiovascular disease: a large prospective cohort study.

The 2017 American College of Cardiology/American Heart Association blood pressure (BP) guidelines lowered the hypertension threshold from a SBP/DBP level of at least 140/90 mmHg to at least 130/80 mmHg. The cardiovascular impact of isolated systolic hypertension (ISH) and isolated diastolic hypertension (IDH) under the new definition remains unclear. We used data from the UK Biobank study, which is a prospective population-based cohort study. Participants were categorized into five groups: normal BP, normal high BP, ISH, IDH and systolic and diastolic hypertension. The primary endpoint for this study was the composite of nonfatal myocardial infarction (MI), nonfatal ischaemic stroke, nonfatal haemorrhagic stroke and cardiovascular disease (CVD) death. We also explored the results for the above-mentioned CVD outcomes separately. Baseline BP measurements were obtained twice after the participant had been at rest for at least 5 min in a seated position. We included 385 955 participants who were not taking antihypertensive medications, were free of CVD at baseline and had available data on BP measurements. During a median follow-up of 8.1 years, 8959 CVD events were recorded, including 4729 nonfatal MIs, 2287 nonfatal ischaemic strokes, 813 nonfatal haemorrhagic strokes, and 1826 CVD deaths. According to the hypertension threshold of at least 130/80 mmHg by the American College of Cardiology/American Heart Association guidelines, both ISH (hazard ratio 1.39; 95% confidence interval 1.27, 1.15) and IDH (hazard ratio 1.28; 95% confidence interval 1.15, 1.43) were significantly associated with a higher overall CVD risk than normal BP. ISH was associated with most CVD risk, except for ischaemic stroke, while the excess CVD risk associated with IDH appeared to be driven mainly by MI and CVD death. We found heterogeneity by sex and age regarding the effects of IDH on overall CVD risk, with significant associations in younger adults (age <60 years) and women and null associations in men and older adults (age ≥60 years). ISH was associated with the risk of most CVD events, while the association between IDH and CVD risk was mainly driven by MI incidence and CVD death. Further research is needed to identify participants with IDH who have a particular risk for developing CVD.

Gestational Diabetes History and Glucose Tolerance After Pregnancy Associated With Coronary Artery Calcium in Women During Midlife: The CARDIA Study.

Gestational diabetes (GD) leads to earlier onset and heightened risk of type 2 diabetes, a strong risk factor for cardiovascular disease (CVD). However, it is unclear whether attaining normoglycemia can ameliorate the excess CVD risk associated with GD history. This study sought to evaluate GD history and glucose tolerance after pregnancy associated with coronary artery calcification (CAC) in women, a manifestation of atherosclerotic CVD and a predictor of CVD clinical events. Data were obtained from the CARDIA study (Coronary Artery Risk Development in Young Adults), a US multicenter, community-based prospective cohort of young Black (50%) and White adults aged 18 to 30 years at baseline (1985-1986). The sample included 1133 women without diabetes at baseline, who had ≥1 singleton births (n=2066) during follow-up, glucose tolerance testing at baseline and up to 5 times during 25 years (1986-2011), GD status, and CAC measurements obtained from 1 or more follow up examinations at years 15, 20, and 25 (2001-2011). CAC was measured by noncontrast cardiac computed tomography; dichotomized as Any CAC (score>0) or No CAC (score=0). Complementary log-log models for interval-censored data estimated adjusted hazard ratios of CAC and 95% confidence intervals for GD history and subsequent glucose tolerance groups (normoglycemia, prediabetes, or incident diabetes) on average 14.7 years after the last birth adjusted for prepregnancy and follow-up covariates. Of 1133 women, 139 (12.3%) reported GD and were 47.6 years of age (4.8 SD) at follow-up. CAC was present in 25% (34/139) of women with GD and 15% (149/994) of women with no GD. In comparison with no GD/normoglycemia, adjusted hazard ratios (95% CIs) were 1.54 (1.06-2.24) for no GD/prediabetes and 2.17 (1.30-3.62) for no GD/incident diabetes, and 2.34 (1.34-4.09), 2.13 (1.09-4.17), and 2.02 (0.98-4.19) for GD/normoglycemia, GD/prediabetes, and GD/incident diabetes, respectively (overall P=0.003). Women without previous GD showed a graded increase in the risk of CAC associated with worsening glucose tolerance. Women with a history of GD had a 2-fold higher risk of CAC across all subsequent levels of glucose tolerance. Midlife atherosclerotic CVD risk among women with previous GD is not diminished by attaining normoglycemia.

Dyslipidemia and Cardiovascular Disease Prevention in South Asians: A Review and Discussion of Causes, Challenges and Management Strategies.

South Asians are at a significantly increased risk of atherosclerotic cardiovascular disease (ASCVD). For a major portion of the South Asian population, the cardiovascular disease events occur at a relatively younger age, are associated with worse outcomes, and have potentially more severe socioeconomic implications compared to their western counterparts. The term "South Asian" typically constitutes individuals from India, Pakistan, Nepal, Bhutan, Bangladesh, Sri Lanka, and Maldives, including expatriates as well as their families from these countries. Based on this, South Asians form approximately 25% of the world's population, with a high ASCVD burden in this group. In this review, we discuss the pathophysiological factors underlying ASCVD in South Asians, the dyslipidemia types and management, and discuss approaches to improve the overall ASCVD prevention efforts in this large subset population of the world. Although the pathophysiological mechanisms underlying the excess risk of cardiovascular disease in South Asians are multifactorial, dyslipidemia is a primary risk factor for the incidence and prevalence of this disease. The traditional "South Asian" dyslipidemia pattern includes levels of low-density lipoprotein cholesterol (LDL-C) in the normal range with a high concentration of LDL particles, elevated triglycerides, low levels of high-density lipoprotein cholesterol (HDL-C) with dysfunctional HDL particles, and high levels of lipoprotein(a). While combined efforts to study the expatriate South Asians in western countries have been able to identify South Asian specific dyslipidemias, causal associations and optimal management remain relatively less explored. Larger scale studies are needed to better quantify the relationship of each lipid parameter with ASCVD risk among South Asians as well as optimal lipid targets and management strategies to reduce morbidity and mortality in this high-risk group.

Prevalence of and Factors Associated With Peripheral Artery Disease in a Population With Chronic Kidney Disease in Australia: A Systematic Review and Meta-analysis

People with chronic kidney disease (CKD) and end stage kidney disease (ESKD) are at excess risk of cardiovascular disease (CVD). However, the prevalence of PAD in Australia is unclear due to different definitions used in the screening.

Glucose-6-Phosphate Dehydrogenase Deficiency Activates Endothelial Cell and Leukocyte Adhesion Mediated via the TGFβ/NADPH Oxidases/ROS Signaling Pathway.

Glucose-6-phosphate dehydrogenase (G6PD) deficiency, the most common genetic inherited trait among humans, affects ~7% of the global population, and is associated with excess risk of cardiovascular disease (CVD). Transforming growth factor-β (TGF-β) regulates immune function, proliferation, epithelial-mesenchymal transition, fibrosis, cancer, and vascular dysfunction. This study examined whether G6PD deficiencies can alter TGF-β-mediated NADPH oxidases (NOX) and cell adhesion molecules (CAM) in human aortic endothelial cells (HAEC). Results show that treatment with high glucose and the saturated free fatty acid palmitate significantly downregulated G6PD; in contrast, mRNA levels of TGF-β components, NOX and its activity, and reactive oxygen species (ROS) were significantly upregulated in HAEC. The expression levels of TGF-β and its receptors, NOX and its activity, and ROS were significantly higher in HG-exposed G6PD-deficient cells (G6PD siRNA) compared to G6PD-normal cells. The protein levels of adhesion molecules (ICAM-1 and VCAM-1) and inflammatory cytokines (MCP-1 and TNF) were significantly increased in HG-exposed G6PD-deficient cells compared to G6PD-normal cells. The adherence of monocytes (SC cells) to HAEC was significantly elevated in HG-treated G6PD-deficient cells compared to control cells. Pharmacological inhibition of G6PD enhances ROS, NOX and its activity, and endothelial monocyte adhesion; these effects were impeded by NOX inhibitors. The inhibition of TGF-β prevents NOX2 and NOX4 mRNA expression and activity, ROS, and adhesion of monocytes to HAEC. L-Cysteine ethyl ester (cell-permeable) suppresses the mRNA levels of TGF-β and its receptors, along with NOX2 and NOX4, and decreases NOX activity, ROS, and adhesion of monocytes to HAEC. This suggests that G6PD deficiency promotes TGF-β/NADPH oxidases/ROS signaling, the expression of ICAM-1 and VCAM-1, and the adhesion of leukocytes to the endothelial monolayer, which can contribute to a higher risk for CVD.

Corrigendum to: Longitudinal Changes in Depressive Symptoms and Risks of Cardiovascular Disease and All-Cause Mortality: A Nationwide Population-Based Cohort Study.

Background There remains a relative paucity of evidence for the association between changes in depressive symptoms with cardiovascular disease (CVD) and mortality. This study aimed to evaluate the association of change in depressive symptoms and incident CVD and mortality in a large prospective cohort of middle-aged and older adults. Methods A total of 6,810 participants free of CVD in the China Health and Retirement Longitudinal Study with two assessments of depressive symptoms at wave 1 (2011-2012) and wave 2 (2013-2014) were included. Elevated depressive symptoms were defined as a score of ≥12 on the 10-item Center for Epidemiologic Studies Depression scale. We used a modified Poisson regression to examine the association of changes in depressive symptoms (never, onset, remitted, and persistent) and incident CVD (a composite endpoint of heart disease or stroke) and mortality at wave 3 (2015-2016). Results During follow-up, 457 CVDs and 148 deaths occurred. Multivariable analyses revealed that persistent depressive symptoms were associated with an elevated risk of CVD (risk ratio = 1.77, 95% confidence interval = 1.38-2.26) and mortality (risk ratio = 1.63, 95% confidence interval = 1.01-2.64) compared with participants without any depressive symptoms. New-onset depressive symptoms increased the mortality risk (risk ratio = 2.37, 95% confidence interval = 1.52-3.69), but not CVD (risk ratio = 1.15, 95% confidence interval = 0.84-1.58). Remitted depressive symptoms were associated with a 35% and 13% excess risk of CVD and mortality, respectively. Conclusion Persistent and remitted depressive symptoms were associated with an increased risk of CVD. New-onset depressive symptoms predicted elevated mortality risk.

Sex differences in the association between myocardial function and prognosis in type 1 diabetes without known heart disease: the Thousand & 1 Study.

In type 1 diabetes mellitus (T1DM), recent findings suggest that women have a greater excess risk of cardiovascular diseases (CVDs) compared to men. Impaired diastolic function is a common feature in T1DM. We investigated the association between myocardial function by echocardiography and outcomes in T1DM males and females without known heart disease. A prospective cohort of individuals with T1DM without known heart disease from the outpatient clinic of Steno Diabetes Center Copenhagen. Follow-up was performed through Danish national registers. Outcomes, major adverse cardiovascular events (MACE) and all-cause mortality, were investigated. A total of 1079 participants (mean age: 49.6 ± 14.5 years, 52.6% male, mean duration of diabetes 25.8 ± 14.6 years) were included in the study. During follow-up (median 6.3 years, interquartile range 5.7-6.9), 142 (13.2%) experienced MACE and 63 (5.8%) died. Gender modified the relationship between E/e' and both MACE and all-cause mortality (P = 0.016 and 0.007, respectively). In females, after multivariable adjustment, both E/e' and global longitudinal strain (GLS) were significantly associated with MACE [E/e': hazard ratio (HR) 1.15 confidence interval (CI) 95%: 1.07-1.24, per 1unit increase; and GLS: HR 1.19 CI 95%: 1.04-1.35, per 1% decrease] and with all-cause mortality (E/e': HR 1.26 CI 95%: 1.11-1.44; and GLS: HR 1.27 CI 95%: 1.03-1.56). In males, the association between E/e' and GLS and outcomes did not reach statistical significance. In female individuals with T1DM both E/e' and GLS provided independent prognostic information, whereas the associations were not significant in males. These results suggest that T1DM affects myocardial function differently in males and females, which may be related to the observed sex difference in CVD risk in T1DM.

Coming out of the PiTs—novel strategies for controlling intestinal phosphate absorption in patients with CKD

The kidneys are the gatekeepers of phosphate balance, and loss of kidney function causes a profound disturbance of mineral metabolism. Patients with chronic kidney disease suffer from an excessive cardiovascular disease risk with a high morbidity and mortality. Current therapies aimed at reducing total phosphate body load are insufficient, and novel strategies are urgently needed. In this issue, Tsuboi and colleagues provide evidence for the use of a novel phosphate transporter inhibitor to reduce intestinal phosphate absorption.

Electrocardiographic abnormalities among people with HIV in Shanghai, China.

People living with HIV (PLWH) have an excess risk of cardiovascular diseases (CVD). Electrocardiographic (ECG) abnormalities are independently predictive of incident cardiovascular events in the general population. Our study aimed to evaluate the prevalence and correlates of ECG abnormalities among PLWH in Shanghai, China. We used a cross-sectional design to collect data from Shanghai Public Health Clinical Center, China. A total of 587 HIV-infected patients aged between 18 and 75 years were recruited between January 2015 and February 2016. The overall prevalence of any type of ECG abnormalities was 53.3%. The prevalence of sinus tachycardia, ST-T segment elevation and left ventricular hypertrophy was 23.0%, 18.1%, and 6.8%, respectively. Multivariable logistic regression analysis indicated that ST-T segment elevation was positively associated with higher baseline HIV viral load (≥ 4 log10 copies/mL), and sinus tachycardia was negatively associated with older age but positively associated with lower CD4 cell count, higher baseline HIV viral load (≥ 4 log10 copies/mL) and higher lactic dehydrogenase (LDH) level (≥133 mg/dL). Any coded ECG abnormality was positively associated with higher baseline HIV viral load (≥ 4 log10 copies/mL). ECG abnormalities including sinus tachycardia and ST-T segment elevation are prevalent among Chinese HIV patients, which are significantly associated with immunodeficiency and HIV viral load. Routine ECG screening may be an important part of HIV clinical care in China.

HIV-1-induced cytokines deplete homeostatic innate lymphoid cells and expand TCF7-dependent memory NK cells.

HIV-1 infection is associated with heightened inflammation and excess risk of cardiovascular disease, cancer, and other complications. These pathologies persist despite antiretroviral therapy (ART). In two independent cohorts, we found that innate lymphoid cells (ILCs) were depleted in the blood and gut of people with HIV-1, even with effective ART. ILC depletion was associated with neutrophil infiltration of the gut lamina propria, type 1 interferon activation, increased microbial translocation, and natural killer (NK) cell skewing towards an inflammatory state with chromatin structure and phenotype typical of WNT transcription factor TCF7-dependent memory T cells. Cytokines that are elevated during acute HIV-1 infection reproduced the ILC and NK cell abnormalities ex vivo. These results demonstrate that inflammatory cytokines associated with HIV-1 infection irreversibly disrupt ILCs. This results in loss of gut epithelial integrity, microbial translocation, and memory NK cells with heightened inflammatory potential, and explains the chronic inflammation in people with HIV-1.

Behavioral risk factors for hypertension among adults living with HIV accessing care in secondary health facilities in Lagos State, Nigeria.

Background:Excess risk for cardiovascular disease, especially hypertension, may exist among human immunodeficiency virus infection (HIV)-positive persons. This study was carried out to assess the prevalence of the behavioral risk factors for hypertension, including their awareness of these factors and their attitudes toward them.Methods:This descriptive cross-sectional study was conducted among 400 HIV-infected adults who accessed care in nine secondary health facilities in Lagos State, Nigeria. Respondents were selected by multistage sampling and data elicited using a structured, interviewer-administered questionnaire. Blood pressure (BP) was measured thrice and a respondent was considered as having raised BP if the mean of the last two measurements is ≥140 mm Hg (systolic BP) or ≥90 mm Hg (diastolic BP) or if respondents are currently taking anti-hypertensive.Results:Prevalence of key behavioral risk factors for hypertension was high. For instance, 82.0% of the respondents were physically inactive. Stress and physical inactivity were the two most known risks of hypertension, identified by 87.3% and 70.5% of the respondents, respectively. Majority (66.0%) had positive attitudes toward hypertension risk factors and 26.7% of them had raised BP. Lower age, that is, 30 years and below (OR = 2.89, 95% CI = 1.26–6.64), BMI of less than 25 (OR = 1.87, 95 CI = 1.16–3.01), and being diagnosed of HIV for 5 years and less (OR = 1.62, 95% CI = 1.006–2.62) were significantly associated with normal BP measurements among respondents.Conclusion:The proportion of people living with HIV/AIDS who show known behaviors that place them at risk for hypertension is high. Measures to address these risk factors among them are warranted.

Work-unit organizational changes and risk of cardiovascular disease: a prospective study of public healthcare employees in Denmark.

The impact of organizational change at work on cardiovascular disease (CVD) among employees is poorly understood. We examined the longitudinal associations between different types of work-unit organizational changes and risk of CVD among employees. We used multilevel mixed-effects parametric survival models to assess the risk of incident ischemic heart disease and stroke (72 events) during 2014 according to organizational changes in 2013 among 14,788 employees working in the same work unit from January through December 2013. We excluded employees with pre-existing CVD events between 2009 and 2013. Data on organizational changes defined as mergers, split-ups, relocations, change in management, employee layoffs, and budget cuts were obtained from work-unit managers (59% response). There was an excess risk of CVD in the year following change in management (HR 2.04, 95% CI 1.10-3.78) and employee layoff (HR 2.44, 95% CI 1.29-4.59) in the work unit relative to no change. Exposure to any organizational change also suggested increased risk of CVD (HR 1.48, 95% CI 0.91-2.43). Including perceived stress as mediator in the regression models attenuated the point risk estimates only slightly, indicating no important mediation through this psychosocial factor. Work-unit organizational change may be associated with excess risk of incident CVD among the employees relative to stable workplaces.

Glucose Management and the Sex Difference in Excess Cardiovascular Disease Risk in Long-Duration Type 1 Diabetes.

The protection against CVD observed in women compared to men in the general population is essentially erased in type 1 diabetes. This review will discuss evidence regarding the role of glucose management on CVD risk by sex, with a particular focus on studies of long-duration type 1 diabetes of > 20years. Across studies, women with type 1 diabetes have similar or worse glycemic control compared to men, despite higher rates of intensive insulin therapy. The association between HbA1c and CVD risk does not seem to differ by sex, but few studies have reported on sex-specific analyses. Beyond HbA1c, there is a lack of published data regarding the relationship between other aspects of glucose management and CVD risk by sex in type 1 diabetes. Glucose management factors do not seem to directly account for the increased CVD risk in women with type 1 diabetes, but may influence other risk factors that play a more direct role.

Association of Lipidomic Profiles With Progression of Carotid Artery Atherosclerosis in HIV Infection

Lipid metabolism disruption and excess risk of cardiovascular disease (CVD) have been observed in HIV-infected individuals, but the associations among HIV infection, plasma lipidome, and CVD risk have not been well understood. To evaluate plasma lipidomic profiles and their associations with carotid artery atherosclerosis in individuals with HIV and individuals without HIV. Prospective analysis in the Women's Interagency HIV Study and Multicenter AIDS Cohort Study during a 7-year follow-up (from 2004-2006 to 2011-2013) at multicenter HIV cohorts in the United States. The study included 737 participants aged 35 to 55 years (520 with HIV and 217 without HIV) without CVD or carotid artery plaque at baseline. Data were analyzed between April 2017 and July 2019. Two hundred eleven plasma lipid species. Poisson regression was used to examine the associations of baseline lipid species with risk of plaque measured by repeated B-mode carotid artery ultrasonography imaging. Of the 737 included participants, 398 (54%) were women, 351 (48%) were African American (non-Hispanic), 156 of 737 (21%) were nonwhite Hispanic, and the mean (SD) age was 45 (6) years. After adjusting for demographic and behavioral factors, we identified 12 lipid species, representing independent signals for 10 lipid classes, associated with risk of plaque. Nine lipid species remained significant after further adjusting for conventional CVD risk factors, although many of them showed moderate to high association with conventional blood lipids (eg, total and low-density lipoprotein cholesterols and triglycerides). Cholesteryl ester (16:1) (risk ratio [RR] per standard deviation, 1.28; 95% CI, 1.08-1.52), ceramide (16:0) (RR, 1.29; 95% CI, 1.02-1.63), lysophosphatidylcholine (20:4) (RR, 1.28; 95% CI, 1.05-1.58), lysophosphatidylethanolamine (16:0) (RR, 1.28; 95% CI, 1.05-1.57), phosphatidylethanolamine (38:6) (RR, 1.33; 95% CI, 1.08-1.64), phosphatidylethanolamine-plasmalogen (36:2) (RR, 1.25; 95% CI, 1.04-1.52), phosphatidylserine-plasmalogen (36:3) (RR, 1.19; 95% CI, 1.00-1.43), and triacylglycerol (54:6) (RR, 1.26; 95% CI, 1.04-1.54) were associated with increased risk of plaque, while phosphatidylcholine (36:4) (RR, 0.65; 95% CI, 0.54-0.77) was associated with decreased risk of plaque. Most of these plaque-increased lipid species showed higher levels in individuals with HIV, particularly among individuals with HIV using antiretroviral therapy compared with individuals without HIV. Network analysis identified 9 lipid modules, and 2 modules composed of triacylglycerols and phosphatidylcholines with long and unsaturated acyl chains, respectively, showed the strongest associations with increased risk of plaque. This study identified multiple plasma lipid species associated with carotid artery atherosclerosis, and alterations in these lipid species might be associated with HIV infection and antiretroviral therapy. Our data suggest unfavorable associations of long-chain and unsaturated triacylglycerols and phosphatidylcholines with carotid artery plaque formation.